Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions
Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions
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DOI：
10.1073/pnas.0502416102
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发表时间：
2005-08-09
影响因子：
11.1
通讯作者：
Wong, GCL
中科院分区：
文献类型：
--
作者：
Liang, HJ;Harries, D;Wong, GCL
基于阴离子脂质（AL）与二价阳离子介导的DNA复合的自组装DNA递送系统由于其低细胞毒性而最近被引入作为阳离子脂质-DNA复合物的替代物。我们研究了不同阳离子诱导的AL-DNA复合物，通过使用同步辐射小角X射线散射和共聚焦显微镜，以显示不同的离子介导的相互作用是如何表达的自组装结构和相行为的AL-DNA复合物。AL-DNA系统中的主导相互作用是复杂的：二价离子可以介导不同组分组合（如DNA-DNA和膜-膜）之间的强吸引力。此外，二价阳离子可以与脂质非静电地配位并改变所得的膜结构。我们发现，在低膜电荷密度AL-DNA复合物组织成一个层状结构的交替DNA和膜层交联的离子。在高膜电荷密度下，观察到在阳离子脂质-DNA系统中没有类似物的新相：DNA从复合物中排出，并形成膜和嵌入离子的层状堆叠。对于一个子集的离子物种，高离子浓度产生一个倒置的六边形相组成的DNA链包裹的离子包被的脂质管。一个简单的理论模型，考虑到静电和膜的弹性贡献的自由能表明，这种转变是一致的离子诱导的变化膜自发曲率，c（0）。此外，层状和倒置六方相之间的交叉发生在临界c（0），与实验值吻合得很好。
Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid-DNA complexes because of their low cytotoxicity. We investigate AL-DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the self-assembled structures and phase behavior of AL-DNA complexes. The governing interactions in AL-DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA-DNA and membrane-membrane). Moreover, divalent cations can coordinate nonelectrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL-DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid-DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature, c(0). Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c(0) that agrees well with experimental values.